Sensei Biotherapeutics Announces Nature Communications Publication Describing Mechanism of Action of SNS-101 Selectively Targeting the Active Form of VISTA within the Tumor Microenvironment

BOSTON, April 04, 2024 (GLOBE NEWSWIRE) -- Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, today announced the publication of a peer-reviewed research paper in Nature Communications. The research was conducted by scientists at Sensei Biotherapeutics in collaboration with genOway and the laboratory of Dr. Robert Schreiber at the Washington University, St. Louis School of Medicine.

The paper describes Sensei Biotherapeutics’ approach to the discovery and development of SNS-101, which was designed to potently and selectively target the active protonated form of VISTA, a protein that plays a significant role in suppressing T-cell activation. VISTA was previously considered undruggable due to its extensive expression on myeloid cells, leading to safety issues such as cytokine release syndrome (CRS), in addition to a pharmacokinetic sink, which poses a significant challenge in reaching therapeutically relevant concentrations. The paper details the mechanism and characteristics of SNS-101, a novel pH-sensitive monoclonal antibody. SNS-101 was shown to bind to a novel epitope of VISTA that is remodeled under low pH conditions, switching VISTA into an active state that engenders extensive T-cell suppression. SNS-101 is designed to block VISTA by inhibiting its interaction with PSGL-1 on T-cells resulting in T-cell activation. Subsequently, in various preclinical models, SNS-101 was shown to mitigate CRS risk and maintain a favorable pharmacokinetic and safety profile, all of which had thwarted the clinical development of first generation, non-pH sensitive anti-VISTA antibodies.   

"The publication of this research in Nature Communications serves as important validation for our tumor-targeting approach and confirms our ability to design highly selective antibodies that target VISTA under the unique conditions of the tumor microenvironment," said Edward van der Horst, Ph.D., Chief Scientific Officer of Sensei Bio. "Our studies of SNS-101 highlight the therapeutic potential for a VISTA-directed immunotherapy unhindered by dose limiting toxicities and off-target effects. We believe the initial clinical data we presented from our Phase 1/2 clinical study further support these important preclinical findings. We are excited to see the impact SNS-101 can have in patients as we advance our ongoing clinical study."